In mammals, meiotic drive is achieved by preferential
segregation of one chromosome over another to the functional
product of female meiosis. Although meiotic drive is a
well-known exception to Mendel's law of segregation, the
molecular mechanisms are not understood. Two components are
required in all meiotic drive systems, the Responder and the
Distorter. The Distorter is the effector in the system, and
“drives” alleles at the Responder. The goal of this
project is molecular identification of the Distorter in the
Om (Ovum mutant) meiotic drive system. Using
recombination mapping we have defined a 300kb candidate
interval for the Distorter locus on mouse chromosome 11. This
locus was named Shade (for Sperm
haploid distorter element). We have
compiled the phenotypes and haplotypes for this region in four
classical strains (C57BL/6J, A/J, DBA2/J, and 129X1/SvJ).
Within the candidate interval there is a 200kb region,
containing four genes, where there is complete
haplotype/phenotype concordance. Interestingly, within the
region of concordance there are two missense mutations and
three UTR mutations. We also characterized the drive phenotype
for 11 additional classical and wild-derived strains. We are
currently completing the haplotypes in the candidate interval
for these additional strains. Based on the level of
haplotype-sharing for these strains observed in other genomic
regions, we expect the reduced size of the candidate interval
to approach one gene and possibly to a single mutation.
Identification of Shade should permit the
characterization of the molecular mechanism behind meiotic
drive, an important evolutionary force in shaping the mammalian
genome.